Process for the production of 4-chloro-6,7-phthaloylquinazoline derivatives

ABSTRACT

Production of 4-chloro-6,7-phthaloylquinazoline derivatives by reaction of 2-acylamino-3-cyanoanthraquinones with hydrogen chloride and phosgene in the presence of N,N-dialkyl carboxylic amides. The 4-chloro-6,7-phthaloylquinazoline derivatives are valuable dyestuff intermediates.

United States Patent Ruske PROCESS FOR THE PRQDUCTION OF 4-CHLORO-6J- Appl. No.: 16,568

Foreign Application Priority Data March 6, 1969 Germany ..P l9 11 305.4

US. Cl. ..260/251 Q Int. Cl. ..C07d 51/48 Field of Search ..260/25 A, 25 Q, 256.4 Q

[ 51 Sept. 26, 1972 [56] References Cited UNITED STATES PATENTS 2,525,380 10/1950 Sutter et al. ..260/2 62 2,530,025 1 l/ 1950 Moergeli et a] ..260/251 2,840,560 6/1958 Sutter ..260/25 6.4

Primary ExaminerAlex Mazel Assistant Examiner-R. V. Rush Attorney-Johnston, Root, O'Keeffe, Keil, Thompson and Shurtleff [5 7] ABSTRACT Production of 4-chloro-6,7-phthaloylquinazoline derivatives by reaction of 2-acylamino-3- cyanoanthraquinones with hydrogen chloride and phosgene in the presence of N,N-dialkyl carboxylic amides. The 4-chloro-6,7-phthaloylquinazoline derivatives are valuable dyestuff intermediates.

5 Claims, No Drawings PROCESS FOR THE PRODUCTION OF 4-COR0 6,7-PHTHALOYLQUINAZOLHNE DERIVA This invention relates to a new and advantageous process for the production of chloroquinazoline derivatives which may be used for example as intermediate for the production of dyes, from 3-cyanoanthraquinones.

A process for the production of 2-phenyl-4chloro- 6,7-phthaloylquinazoline is described in US. Pat. No.

according to which 2- benzoylaminoanthraquinone-3-nitrile is treated in an inert solvent or diluent with phosphorus pentachloride at a temperature rising from 1 to 185C.

This known method has the disadvantage that the reactants are partly decomposed under the extreme reaction conditions and in consequence the chloroquinazoline derivative is contaminated by phosphorus compounds, which interferes with the further processing of the product, for example into dyes.

Since moreover the use of phosphorus pentachloride in industry offers difficulties owing to the hydroscopic properties and strongly corrosive action of this compound and since the solvent used in the reaction can only be recovered by troublesome operations, a process for the production of chloroquinazoline derivatives in which the said disadvantages are avoided has been much sought after.

I have now found that chloroquinazoline derivatives can be prepared particularly advantageously by treating a 3-cyanoanthraquinone which contains an acylated amino group in the 2-position in an inert solvent or diluent with at least a molar amount (with reference-to the 3-cyanoanthraquinone) of hydrogen chloride and phosgene at a temperature of from 50 to 150C, preferably from 90 to 105C, in the presence of an N,N- disubst'ituted carboxylic amide.

Compounds which bear an acetylamino or benzoylamino group in the 2-position are suitable as 3- cyanoanthraquinones. The following 3- cyanoanthraquinones aregiven by way of example:

2-benzoylamino-3-cyanoanthraquinone,

2-acetylamino-3-cyanoanthraquinone, 2-(4'-chlorobenzoylamino)-3-cyanoanthraquinone,

2-( 3 '-bromobenzoylamino )-3-cyanoanthraq uinone,

2-( 3 '-trifluoromethylbenzoylamino )-3- cyanoanthraquinone and 2-(4'-phenylbenzoylamino)-3-cyanoanthraquin one. Of these compounds, 2-benzoylamino-3- cyanoanthraquinone is of particular industrial interest as starting material.

Both hydrogen chloride and phosgene are used in at least molar amounts with reference to 3- acylaminoanthraquinone. It is advantageous to use these gases in excess, for example in 1.2 to times the molar amount, the ratio of hydrogen chloride to phosgene being kept approximately in the ratio of their molecular weights.

- The inert solvent or diluent should be anhydrous. It is preferably used in excess in order to ensure satisfactory distribution of the phosgene and hydrogen chloride in the reaction mixture. Since soluble intermediate stages are formed during the reaction, an amount of 5 to 15 times that of the 3-acylaminoanthraquinone, is generally sufficient. Examples of suitable solvents or diluents are nitrobenzene, chlorobenzene, orthodichlorobenzene, trichlorobenzene and toluene.

The 3-acylaminoanthraquinone according to the new process is treated in the said solvent or diluents at temperatures of from 50 to 150C, preferably from to C, with hydrogen chloride and phosgene in the presence of N,N-substituted carboxylic amide. The following N,N-disubstituted carboxylic amides are given as examples: N,N-dimethylformamide, N,N-diethylformamide, N,N-dibutylformamide, N,N-diethylacetamide, N,N-dimethylpropionamide and N,N-dimethylbenzarnide. These disubstituted carboxylic amides may be used for example in 0.1 to 1 molar amount with reference to 3-acylaminoanthraquinone.

The reaction is over within about two to ten hours in the preferred temperature range of from 90 to 105C. The chloroquinazoline derivative may be isolated (after excess phosgene has been removed) for example by cooling the reaction mixture to 20 to 30C, the product being suction filtered and dried, remainders of solvents which are not volatile being removed for example by washin g with methanol.

Since chloroquinazoline derivatives are prepared in high purity by the new process, the said processing may be omitted in many cases and the chloroquinazoline may be used for further reactions either after partial or EXAMPLE 1 One thousand twenty parts of nitrobenzene, 130 parts of 2-benzoylamino-3-cyanoanthraquinone and 14.6 parts of N,N-dimethylformamide are heated at 80C in a stirred pressure vessel having two gas inlet pipes for hydrogen chloride and phosgene and a reflux condenser having brine cooling. While the temperature is rising from 80 to 95C, 5 parts of hydrogen chloride and 14.3 parts of phosgene are passed in per hour within 1 hour at 80 to 95C and within 4 hours at 95 to 98C. The excess phosgene is blown off with nitrogen. The reaction mixture is cooled to 20C and suction filtered through a filter stone. The residue is washed with nitrobenzene and methanol in portions and dried at 90C. About parts (91.2 percent of the theory) of 2-phenyl-4-chloro6,7-phthal0ylquinazoline is obtained having a chlorine number of about 9.4 percent.

According to US. Pat. No. 2,530,025 only 76 percent of the theory of 2-phenyl-4-chlor0-6,7- phthaloylquinazoline is obtained (with reference to the 2-benzoylamino-3-cyanoanthraquinone) of which the analysis is: calculated for C H ONCI C 68.9 H 3.3 011.5 N 7.7 CI 8.6 P 0.8 found: 71.2 2.96 8.65 7.55 9.6

EXAMPLE 2 Seventy parts of 2-benzoylamino-3- EXAMPLE 3 Eight hundred parts of nitrobenzene and 85.6 parts of 2-(4'-phenylbenzoylamino)-3-cyanoanthraquinone are heated to 95C in a stirred pressure vessel. 9.5 parts of N,N-dimethylformamide is introduced at this temperature. Twenty parts of phosgene and 7 parts of hydrogen chloride are introduced per hour while mixing well. The internal temperature is raised in 30 minutes to 105 to l 10C and kept for 5 to 6 hours at 110 to 115C. Excess phosgene is blown out with nitrogen. The reaction mixture is worked up as described in Example 1. Seventy-four parts of 2-(4- phenyl)phenyl-4-chloro 6,7-phthaloylquinazoline is obtained having a chlorine number of 7.9 percent (calculated 7.85 percent) and a melting point of 290 to 291C.

EXAMPLE 4 A mixture of 350 parts of nitrobenzene and 38.6 parts of 2-(4'-chlorobenzoy1amino)-3- cyanoanthraquinone is heated to 80C and parts of N,N-diethylformamide is added. While mixing well, 10 parts of phosgene and 3.6 parts of hydrogen chloride are passed in per hour and the temperature is kept for 6 hours at 100 to 105C. Excess phosgene is expelled with nitrogen and the mixture is worked up analogously to Example 1. 32 to 33 parts of 4,4'-dichloro-2-phenyl- 6,7-phthaloylquinazoline is obtained having a chlorine content of about 16 percent.

EXAMPLE 5 Three parts of N,N-dimethylformamide is added at 80C to a mixture of 280 parts of nitrobenzene and 27.4 parts of 2-(3-methylbenzoylamin0)-3- cyanoanthraquinone. The whole is heated to 90C and then for 5 to 6 hours at 100 to 105C, 10 parts of phosgene and 3.6 parts of hydrogen chloride being introduced per hour. The dissolved reaction product is precipitated when the excess phosgene is expelled and the reaction mixture is cooled to 15 to 20C. 18 parts of 2-(3'-toly1)-4-chloro-6,7-phthaloylquinazoline is obtained having a melting point of 256 to 257C.

EXAMPLE 6 41.9 parts of 2-( 3-trifluoromethylbenzoylamino)-3- cyanoanthraquinone and 5 parts of N,N-dimethylformamide are introduced at C into 500 parts of nitrobenzene. The whole is heated to C and 15 parts of phosgene and 5.4 parts of hydrogen chloride are passed in per hour. The reaction period is 5 to 6 hours at to C. The phosgene is expelled and the product 15 isolated as described in the foregoing Examples. 19.4 parts of 2-(3'-trifluoromethylphenyl)-4- chloro-6,7-phthaloylquinazoline is obtained having a melting point of 227 to 228C.

lclaim:

l. A process for the production of a 4-chloro-6,7- phthaloylquinazoline derivative which comprises treating a 2-cyanoanthraquinone substituted in the 2-position by acetylamino, benzoylamino or benzoylamino which is further substituted in its phenyl ring in the 3 or 4 position by chlorine, bromine, phenyl, methyl or trifluoromethyl, while in an anhydrous inert diluent with at least a molar amount, with reference to the 3- cyanoanthraquinone, of hydrogen chloride and phosgene at a temperature of from 50 to C. in the presence of an N ,N-dialkyl carboxylic amide having 1 to 4 carbon atoms in each alkyl group and a carboxylic residue derived from an alkanoic acid of 1 to 3 carbon atoms or benzoic acid.

2. A process as claimed in claim 1 carried out at a temperature of from 90 to 105C.

3. A process as claimed in claim 1 wherein N ,N- dimethylformamide is used as the N,N-disubstituted carboxylic amide.

4. A process as claimed in claim 1 wherein 2- benzoylamino-3-cyanoanthraquinone is used as the 3- cyanoanthraquinone.

5. A process as claimed in claim 1, wherein the N-N- dialkylcarboxylic amide used is selected from the group consisting of N,N-dimethylformamide, N,N-diethylformamide, N,N-dibutylformamide, N,N-diethylacetamide, N,N-dimethylpropionamide and N-N-dimethylbenzamide. 

2. A process as claimed in claim 1 carried out at a temperature of from 90* to 105*C.
 3. A process as claimed in claim 1 wherein N,N-dimethylformamide is used as the N,N-disubstituted carboxylic amide.
 4. A process as claimed in claim 1 wherein 2-benzoylamino-3-cyanoanthraquinone is used as the 3-cyanoanthraquinone.
 5. A process as claimed in claim 1, wherein the N-N-dialkylcarboxylic amide used is selected from the group consisting of N,N-dimethylformamide, N,N-diethylformamide, N,N-dibutylformamide, N,N-diethylacetamide, N,N-dimethylpropionamide and N-N-dimethylbenzamide. 